Design, Synthesis and Biological Evaluation of Salicylamide Analogues as Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Abstract

Blocking epidermal growth factor receptor (EGFR) has been the hotspot in the field of cancer therapy. Based on the fact that salicylanilides possess well inhibitory activity against EGFR tyrosine kinase, a series of salicylamide analogs bearing 4’-substitution were designed to explore new candidates exhibiting improved efficacy against EGFR. Many of the synthesized compounds inhibited EGFR in the micromolar range, especially compounds 15a and 15b (IC50 = 0.27 μM and 1.1μM, respectively). We report our findings as a basis for further development in salicylamide analogues as EGFR inhibitors. Keywords: EGFR inhibitors, in vitro enzyme assay, synthesis, molecular modeling, salicylamides, structure–activity relationships.